1. Peptic Ulcer Disease Biol E-163 12/11/06

2. From: Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

3. Peptic Ulcer Erosion in a segment of the GI mucosa that penetrates through the muscularis mucosae gastric antrum ulcer duodenal bulb ulcer that is bleeding From: Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

4. Etiology 1.H. pylori infection –70-90% of gastric ulcers –80-90% of duodenal ulcers 2.NSAID use 3.Cigarette smoking –Increased risk of developing ulcers –impairs healing –increases incidence of recurrence 4.Family history –May reflect genetic susceptibility or intrafamilial H. pylori infection

5. Pathogenesis Associated with amount of acid and degree of activation of pepsinogen within the gastric lumen –Pepsinogen = precursor to protein-digesting enzyme that is activated to pepsin by the acid environment of the stomach Mechanism of H. pylori: –Not understood why/how infection weakens the gastric mucosal layer to be damaged by acid Mechanism of NSAID use: –Inhibition of prostaglandin synthesis –Prostaglandins stimulate mucus and bicarbonate secretion, and enhance surface hydrophobicity –Can also increase risk of gastric bleeding by interfering with platelet function (necessary for blood clotting)

6. Symptoms Depend on ulcer location and age –Pain (most common) often relieved by antacids usually chronic and recurrent –Many patients have few or no symptoms especially the elderly –Gastric ulcers inconsistent pattern of symptoms eating can either ameliorate or exacerbate symptoms –Duodenal ulcers more consistent pain common at night and relieved by food

7. Diagnosis Patient history Confirmed by endoscopy –Biopsy ulcer to determine if malignant –Definitively diagnose H. pylori infection

8. Complications (1) 1.Hemorrhage –Vomiting of blood or passage of bloody stool 2.Penetration –Penetrates stomach wall but does not leak into peritoneal cavity –Intense persistent pain –Diagnosis confirmed by CT or MRI 3.Free perforation –Perforates the stomach wall and into peritoneal cavity –Sudden, intense, continuous gastric pain that spreads throughout abdomen –Shock may occur, characterized by increased pulse rate, decreased BP, decreased urine output –Diagnosis confirmed by x-ray (free air space under diaphragm or peritoneal cavity)

9. Complications (2) 4.Gastric outlet obstruction –Caused by scarring, spasm, or inflammation from ulcer –Recurrent, large-volume vomiting, often at end of day –Diagnosis confirmed by physical exam, gastric aspiration (>200 mL fluid after fasting overnight), or x-ray 5.Recurrence –Common risk factors: persistant H. pylori infection, NSAID use, smoking –1-yr recurrence rate is 60% when it is not 6.Stomach cancer –People with H. pylori-associated ulcers have 3 to 6 fold increased chance of malignancy later in life –No increased risk of cancer for ulcers associated with other etiologies

10. Treatments 1.Reduce gastric acidity –Histamine, acetylcholine, and gastrin stimulate HCl secretion from parietal cells –Histamine (H 2 ) antagonists: reduce histamine production, which also blocks effects of acetylcholine, and gastrin 2.Antibiotics to rid H. pylori infection 3.Discontinue smoking 4.Surgery –Last resort –Most applicable to complications that don’t respond to drug therapy (for example: penetration, free perforation, obstruction) –Procedure involves reduction of acid secretion and while ensuring gastric drainage

11. Symptoms After Surgery (1) After resective surgery, up to 30% of patients have significant symptoms 1.Weight loss 2.Maldigestion 3.Anemia (iron or vitamin B 12 deficiency) 4.Dumping syndrome –Weakness, dizziness, sweating, nausea, vomiting, and palpitation that occurs soon after eating

12. Symptoms After Surgery (2) 5.Reactive hypoglycemia (aka late dumping) –Rapid emptying of carbs from the gastric pouch –High peaks in glucose stimulate over-release of insulin  hypoglycemia several hours after meal 6.Mechanical problems –Decrease in motor contractions –Diarrhea 7.Ulcer recurrence